This invention relates to a method for prevention or treatment of ischemia reperfusion injury or multi-organ failure in an individual by administering to said individual an effective amount of an interferon beta.
The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference.
Several conditions, including abdominal injuries, bowel infraction, cardiovascular surgery and shock, can lead to intestinal ischemia-reperfusion injury (IRI). Importantly, besides causing local injury IRI also triggers systemic inflammatory response in remote organs resulting in a syndrome called multi-organ failure. In this syndrome lungs are especially vulnerable. The most prominent signs of the injury are increased vascular permeability (vascular leakiness) and neutrophil accumulation. The lung injury subsequent to intestinal IRI is primarily due to release of pro-inflammatory cytokines in the gut. Intestinal IRI increases intestinal permeability with subsequent release of bacterial endotoxin that promotes systemic inflammation in multi-organ failure. Also other mediators released from activated neutrophils play an important role.
CD73 (ecto-5′-nucleotidase, 5′-NT) is a glycoprotein expressed on the surface of lymphocytes and endothelial and epithelial cells. CD73 regulates leukocyte adhesion via its enzymatic function. It catalyzes hydrolysis of AMP to adenosine. Adenosine produced by CD73 decreases vascular permeability and neutrophil sequestration in hypoxic tissue. However, the role of CD73 in distant organ injury in IRI is not known.
Due to the central role of vascular leakage in IRI, molecules regulating the permeability changes via adenosine or by other mechanisms may be potential targets to combat multi-organ failure. Since interferon beta is known to both induce CD73 expression (and adenosine production) and has other immunomodulatory effects, we studied its utility in distant organ injury in multi-organ failure.